Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.
Level 3 - non-randomized controlled study
Multicentre prospective longitudinal cohort study
PubMed 38823406 · doi:10.1016/S0140-6736(24)00596-8
What was done
The ORFAN multicentre longitudinal cohort study evaluated 40,091 consecutive patients undergoing clinically indicated coronary computed tomography angiography (CCTA) across eight UK NHS hospitals, followed for major adverse cardiac events (MACE: myocardial infarction, new-onset heart failure, or cardiac death) over a median of 2.7 years (IQR 1.4–5.3). Prognostic performance of the perivascular fat attenuation index (FAI) Score was analyzed in a subcohort of 3,393 consecutive patients from two centres followed for a median of 7.7 years (IQR 6.4–9.1). An AI-Risk prognostic algorithm integrating FAI Score, plaque metrics, and clinical risk factors was externally validated.
What was found
Patients without obstructive coronary artery disease (CAD) represented 81.1% of the cohort (32,533 of 40,091) and accounted for 66.3% of total MACE (2,857 of 4,307) and 63.7% of cardiac deaths (1,118 of 1,754). Elevated FAI Score across all three coronary arteries carried substantial risk for cardiac mortality (hazard ratio [HR] 29.8, 95% CI 13.9–63.9, p<0.001) and MACE (HR 12.6, 95% CI 8.5–18.6, p<0.001) comparing top versus bottom quartiles. The AI-Risk tool predicted cardiac mortality (HR 6.75, 95% CI 5.17–8.82, p<0.001, very high vs low/medium risk) and MACE (HR 4.68, 95% CI 3.93–5.57, p<0.001) independently of traditional risk factors and CAD severity.
Why it matters
Most cardiac events occurred in individuals without obstructive CAD who lack clear risk stratification. Imaging perivascular inflammation via CCTA provides strong prognostic value beyond conventional anatomical stenosis and standard clinical risk calculators.
Limits
The study is observational and cannot demonstrate whether treatment adjustments triggered by FAI or AI-Risk scoring improve patient outcomes. The long-term FAI analysis was restricted to 3,393 patients across only two centres. Findings in symptomatic UK NHS patients referred for CCTA may not generalize to broader asymptomatic populations or non-UK healthcare systems.
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- supports Pericoronary arterial inflammation detected by AI analysis on CT angiography in the absence of arterial narrowing is associated with up to a 15-fold increased risk of heart attack.